It
is my hypothesis that human evolution is driven by increases in
testosterone in the population with time. ("Androgens in Human
Evolution," Rivista di Biologia / Biology Forum 2001; 94:
345-362. If your library does not subscribe to "Rivista ... ,"
you may find this at:
http://anthropogeny.com/Androgens%20in%20Human%20Evolution.htm .)

The
mechanism of testosterone effects is increased entrance of DHEA into
cells because of increased androgen receptors which occurred with the
increase of testosterone. Human evolution is an extension of
mammalian evolution. ("Hormones in Mammalian Evolution,"
Rivista di Biologia / Biology Forum 2001; 94: 177-184. If your
library does not subscribe to "Rivista ... ," you may find
this at:
http://anthropogeny.com/Hormones%20in%20Mammalian%20Evolution.htm .)

The
natural reduction in testosterone reduces the production of androgen
receptors which, therefore, reduces DHEA effects in cells.

Reduced
entrance of DHEA into cells reduces the activity GLUT1 (glucose
transporter 1). It has been determined that DHEA stimulates transport
of GLUT1 to the cell surface where it transports glucose into the
cell, therefore, keeping plasma glucose levels "normal."
High plasma glucose is the hallmark of type 2 diabetes.

(My
explanation of human evolution suggests that periodically
testosterone increases substantially. This causes a problem with high
testosterone. I think we are currently in one of those periods which
results in a high, early peak of testosterone followed by an early,
deep decline in testosterone during the life span.

It
is my hypothesis that evolution selected dehydroepiandrosterone
because it optimizes replication and transcription of DNA, that is,
genes. Therefore, DHEA levels affect all tissues and all tissues
compete for available DHEA, especially the brain. (I think
evolutionary selection of DHEA produced mammalia. "Hormones in
Mammalian Evolution," Rivista di Biologia / Biology Forum 2001;
94: 177-184,
http://anthropogeny.com/Hormones%20in%20Mammalian%20Evolution.htm ).
DHEA naturally begins to decline around the ages of twenty to
twenty-five, reaching very low levels in old age. When DHEA is low or
decreasing, all tissues are adversely affected; when DHEA is too low,
death occurs.

Type
2 diabetes often produces pathological changes in various tissues. I
suggest that these diabetes-associated diseases are caused by the
loss of DHEA, as in high plasma glucose. Loss of DHEA adversely
affects gene activation in other tissues which appear as these
symptoms. For example: “...skeletal muscle tissue GLUT1 protein
expression is reduced in type 2 diabetes...” (J Clin Endocrinol
Metab. 2005 Jan;90(1):352-8) and for contrast in normal tissue: Nutr
Metab (Lond). 2012 May 30;9:47 and Am J Physiol Endocrinol Metab.
2008 May;294(5):E961-8. Obesity is often named as the cause of T2
diabetes and other phenomena which are also all increasing
simultaneous with T2 diabetes. Low DHEA / low testosterone expose
less than optimally functioning genes when these two androgens
naturally decline (early onset diseases) and when their production is
so low that optimally functioning genes are affected (late onset
diseases).

I
am not satisfied that treatment of glucose levels will "cure"
type 2 diabetes.

It
is also my hypothesis that low DHEA is involved in cancer initiation.
In 1994, I first suggested that low DHEA is directly involved in
initiation of oncogenes: "An Explanation of Cancer and the
Increase in Cancer: High Testosterone, Low DHEA and Breast Cancer,"
at:
http://anthropogeny.com/An%20Explanation%20of%20Cancer%20and%20the%20Increase%20in%20Cancer.htm
which appeared first in publication: Annals of Internal Medicine
2005; 142: 471-472 . This may explain the "Epidemiological bases
and molecular mechanisms linking obesity, diabetes, and cancer,"
(Endocrinología, Diabetes y Nutrición (English ed.) Volume 64,
Issue 2, February 2017, Pages 109–117). The natural decline of
estradiol may exert a similar effect.)

I
suggest the base cause of type 2 diabetes is loss of available DHEA
for gene function, precipitated by the loss of testosterone.